Vicinal diamines are compounds which contain amino groups on adjoining positions on a carbon structure. The vicinal diamine group is commonly observed in naturally occurring compounds and plays an important role in medicinal chemistry, particularly in metal chelation. Despite the importance of this functional group, few general diamination methods exist. Furthermore, those methods that do exist are limited regarding their ability to include other functional groups on the molecule.
Vicinal diamines are most commonly prepared from olefins. Direct reaction of olefins with azide anion gives rise to vicinal diazides under electrochemical oxidation or transition metal oxidation with Mn(III), Fe(III), or Pb(IV). Alternatively, vicinal diazides can be prepared from epoxides via hydroxyazide intermediates or from vicinal dihalides via bimolecular nucleophilic substitution (referred to as "Sn2") reactions. The vicinal diazides can be reduced to amines; however, vicinal diazides are prone to many side reactions during reduction and require careful selection of reductants. Azides always present a possible explosion hazard as well.
There are less direct methods of preparing vicinal diamines from olefins. One such method converts olefins to iodocarbamates in a rather cumbersome manner involving iodoisocyanation and methanolysis of the isocyanate. Treatment of the iodocarbamate with hydroxide results in the formation of an aziridine which can be opened with ammonia to give vicinal diamines stereospecifically. Another method involves cycloaddition of chlorosulfonyl isocyanate to the olefin followed by a Curtius rearrangement and hydrolysis of the resulting cyclic urea. A third method involves the preparation of vicinal diamines from olefins and cyanamide/N-bromosuccinimide. A fourth method using olefins involves preparation from dienes via a Diels-Alder adduct of sulfur dioxide bis-imides.
Other methods of preparing vicinal diamines include reductive amination of an .alpha.-amino ketone, Michael addition of a urethane to a dehydroalanine derivative, reduction of .alpha.-amino nitriles which are prepared ultimately from aldehydes, and reduction of .alpha.-amino amides derived from amino acids.
In summary, the current methods of preparing vicinal diamines have a number of problems, including cumbersomeness, safety hazards, and limitations on how complex the product can be. Thus, there is a need in the art for a synthesis of vicinal diamines which is convenient, avoids azides, and allows for incorporation of a variety of functional groups. The present invention fulfills this need and further provides other related advantages.